EP2153401B1 - System and method for quality assurance in pathology - Google Patents
System and method for quality assurance in pathology Download PDFInfo
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- EP2153401B1 EP2153401B1 EP08747494.6A EP08747494A EP2153401B1 EP 2153401 B1 EP2153401 B1 EP 2153401B1 EP 08747494 A EP08747494 A EP 08747494A EP 2153401 B1 EP2153401 B1 EP 2153401B1
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- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H30/00—ICT specially adapted for the handling or processing of medical images
- G16H30/20—ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B21/00—Microscopes
- G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
- G02B21/365—Control or image processing arrangements for digital or video microscopes
-
- G—PHYSICS
- G06—COMPUTING OR CALCULATING; COUNTING
- G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G06T7/00—Image analysis
- G06T7/0002—Inspection of images, e.g. flaw detection
-
- G—PHYSICS
- G06—COMPUTING OR CALCULATING; COUNTING
- G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G06T7/00—Image analysis
- G06T7/0002—Inspection of images, e.g. flaw detection
- G06T7/0012—Biomedical image inspection
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- G—PHYSICS
- G06—COMPUTING OR CALCULATING; COUNTING
- G06V—IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING
- G06V10/00—Arrangements for image or video recognition or understanding
- G06V10/98—Detection or correction of errors, e.g. by rescanning the pattern or by human intervention; Evaluation of the quality of the acquired patterns
- G06V10/987—Detection or correction of errors, e.g. by rescanning the pattern or by human intervention; Evaluation of the quality of the acquired patterns with the intervention of an operator
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- G—PHYSICS
- G06—COMPUTING OR CALCULATING; COUNTING
- G06V—IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING
- G06V20/00—Scenes; Scene-specific elements
- G06V20/60—Type of objects
- G06V20/69—Microscopic objects, e.g. biological cells or cellular parts
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- G—PHYSICS
- G06—COMPUTING OR CALCULATING; COUNTING
- G06V—IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING
- G06V20/00—Scenes; Scene-specific elements
- G06V20/60—Type of objects
- G06V20/69—Microscopic objects, e.g. biological cells or cellular parts
- G06V20/693—Acquisition
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- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H40/00—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices
- G16H40/20—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the management or administration of healthcare resources or facilities, e.g. managing hospital staff or surgery rooms
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- G—PHYSICS
- G06—COMPUTING OR CALCULATING; COUNTING
- G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G06T2207/00—Indexing scheme for image analysis or image enhancement
- G06T2207/10—Image acquisition modality
- G06T2207/10024—Color image
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- G—PHYSICS
- G06—COMPUTING OR CALCULATING; COUNTING
- G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G06T2207/00—Indexing scheme for image analysis or image enhancement
- G06T2207/10—Image acquisition modality
- G06T2207/10056—Microscopic image
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- G—PHYSICS
- G06—COMPUTING OR CALCULATING; COUNTING
- G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G06T2207/00—Indexing scheme for image analysis or image enhancement
- G06T2207/30—Subject of image; Context of image processing
- G06T2207/30004—Biomedical image processing
- G06T2207/30024—Cell structures in vitro; Tissue sections in vitro
Definitions
- the present invention generally relates to pathology and microscopy and more particularly relates to improvements in quality assurance for pathology using digital microscopy.
- a flow diagram illustrating a conventional process for quality assurance using glass slides is shown.
- a glass slide is prepared and then in step 110 the quality of the slide is inspected and assessed.
- a histotechnologist screens the glass slides to assess slide quality, as shown in step 120, and rejects sub-optimal slides before they are read by a pathologist.
- Rejected slides result in re-cuts and the preparation of new, presumably higher quality, glass slides.
- the slides can be fixed, e.g., by restaining if the staining is too light. This is shown in step 130.
- the slide is reviewed and interpreted by a pathologist in step 140.
- This conventional process suffers from the inability of the histotechnologist to carefully review every area of a glass slide (some labs process hundreds or thousands of slides every day).
- the conventional process additionally suffers from the increasing shortage of qualified histotechnologists, and pressure on laboratories to continually improve productivity.
- the overall aging of the population and the associated increased incidence of cancer (and surgical biopsies) only exacerbate the challenges of quality-assuring glass slides before they are read by a pathologist due to the significant increase in the number of glass slides that are prepared.
- US 2006/007345 A1 discloses a system and a method for assessing virtual microscope slide image quality, wherein in order to determine whether a virtual slide image has any out of focus areas and is therefore a candidate for manual inspection, the various focus points used to scan the virtual slide image are used to calculate a best fit surface for the virtual slide image and the distance of each focus point from the best fit surface is then calculated and the largest distance is compared to a predetermined value.
- the present invention provides a computer implemented method for improved image quality assurance in pathology as defined in claim 1. Further embodiments of the method according to the present invention are described in the dependent claims.
- Digital slides created by slide scanning instruments contribute to improved diagnosis by pathologists by providing an automatic, systematic, objective, and consistent means for digital slide creation and analysis, enabling the use of computer implemented image analysis and image correction tools.
- a digital pathology system assesses and improves the quality of a digital slide.
- the improved digital slide has a higher image quality that results in increased efficiency in the interpretation of such digital slides when they are viewed on a monitor by a pathologist.
- These improved digital slides yield a more objective diagnosis than reading the corresponding glass slide under a microscope.
- FIG. 2 is a flow diagram illustrating a process for quality assurance using digital slides.
- the illustrated process can be carried out by a digital pathology system such as that later described with respect to FIG. 5 .
- the glass slide is prepared in the conventional manner.
- the glass slide is scanned (digitized) to create a high quality digital slide image of the glass slide at a diagnostic resolution for the tissue type.
- computer implemented digital slide analysis tools are automatically applied to the slide in step 220 to assess the quality of the digital slide image.
- the color and focus of a digital slide can be analyzed by quality modules that consider image attributes that include the contrast, brightness and spatial resolution of individual and groups of pixels in the digital slide image.
- the corresponding glass slide can be rejected and an operator can prepare a new glass slide. If the quality of the digital slide is sufficient for diagnosis, as determined in step 230, then the digital slide can be analyzed and interpreted by a pathologist, who views the digital slide on the monitor at a local or remote viewing station. Alternatively, glass slides in which the quality of the corresponding digital slide is determined to be sufficient by the computer implemented digital slide analysis tools, could be interpreted by a pathologist using a microscope.
- the digital slide quality assessment is made by comparing objective characteristics of the digital slide against a predetermined set of criteria.
- this provides a consistent and standard level of quality in any digital slide image that can be systematically applied to all digital slides destined for review by a pathologist.
- the digitizing and automatic assessment of the digital slide may be employed for the sole purpose of removing this task from the histotechnologist, thereby allowing that person to perform other tasks and improve efficiencies.
- the histologist may be notified of borderline quality slides in order to make the final determination of quality for a significantly fewer number of glass slides.
- FIG. 3 is a flow diagram illustrating an alternative process for quality assurance using digital slides.
- the illustrated process can be carried out by a digital pathology system such as that later described with respect to FIG. 5 .
- the process in FIG. 3 is initially similar to the process described with respect to FIG. 2 so only the differences will be described here.
- the digital slide image can be rejected and an operator can rescan the glass slide.
- This can be more efficient if, for example, the digital slide image was rejected due to problems with focus or even problems with too much staining.
- a rescan of a glass slide with too much staining can be done with decreased light during scanning in order to account for the over staining.
- this saves significant time in the overall process and also saves the native tissue source and other goods used in glass slide preparation.
- step 330 the system next applies computer implemented digital slide enhancement tools to improve the quality of the digital slide image even further, as shown in step 340.
- the colors of stains can be enhanced or even changed to provide more color contrast in counterstained samples.
- step 350 the digital slide can be analyzed and interpreted by a pathologist, who views the digital slide on the monitor at a local or remote reviewing station.
- the improved digital slide is fed into a clinical decision support system that guides the pathologist through the process of making an interpreting the slide in order to arrive at a diagnosis for the slide, or the case associated with the slide.
- step 320 A few variations in the process shown in FIG. 3 are also possible. For example, if the image quality of the digital slide as determined in step 320 is poor then a new glass slide maybe prepared rather than rescanning the original glass slide. Additionally, providing digital enhancements to the digital slide image is not a necessary step in the process although it provides potentially significantly improved images and can facilitate a more accurate diagnosis by the pathologist.
- the quality assurance system described herein includes using the slide scanning instrument to assess the quality of the glass slide being scanned, and in the event that the glass slide fails predetermined quality criteria, the scanning parameters of the scanning instrument are modified to create a digital slide with improved quality. A slide that is over stained (too dark) would be automatically re-scanned with less light.
- the determination of whether the glass slide meets predetermined quality criteria can be achieved by initially scanning the glass slide at low or high power and then performing certain types of image analysis on the resulting image to determine, as in the above example, if the slide is too dark.
- FIG. 4 is a flow diagram illustrating an alternative process for quality assurance using digital slides according to an embodiment of the invention.
- the illustrated process can be carried out by a digital pathology system such as that later described with respect to FIG. 5 .
- a glass slide is digitized and then in step 410 the digital slide is automatically evaluated against a set of predetermined criteria to assess the digital slide quality.
- slides that meet or exceed the objective baseline for digital slide quality are then digitally enhanced where possible and then the digital slide is provided to a pathologist for review and analysis, as shown in step 430.
- FIG. 4 is a highly streamlined computer implemented process.
- a plurality of slides may be provided to the digital microscopy system for automatic serial or parallel scanning that results in the digital slides being provided to a local or remote pathologist for analysis and diagnosis.
- examples of the types of enhancements made in step 420 to improve the digital slide image prior to diagnosis by a pathologist include enhancement of contrast, color, elimination of defects, and the like including other image processing techniques.
- color space standardization can be used to transform the digital slide image into a standardized or non-standardized (and better) color space. Doing so can ensure that digital slides displayed on a monitor appear more consistent in color than the corresponding glass slides would appear under a microscope.
- image processing can apply image enhancement filters (e.g., sharpening, deconvolution, etc.) to the digital slide to enhance spatial details that are not readily apparent to the naked eye.
- quality assessments can be computed to provide the pathologist an objective computer-generated measure of digital slide quality that informs the pathologist about the underlying integrity of the digital slide. This can be particularly advantageous to a pathologist because knowing that the digital slide quality is suboptimal (e.g., because of poor sample preparation) can be helpful to a pathologist. For example, if the result of a diagnosis of a suboptimal digital slide required surgery, the pathologist may instead order a new glass slide to be prepared and digitized in order to conduct a second review and analysis of the tissue.
- Image pattern recognition can also be employed, for example, as part of a decision support system, to automatically identify for a pathologist those regions of a digital slide which have diagnostic significance. This can be very helpful and provide a pathologist with the ability to interrogate regions of one or more digital slides in priority order. Additionally, content based image retrieval can be extremely useful by providing the pathologist with previously diagnosed (i.e., "solved" cases) that have similar image patterns to the digital slide being analyzed. In one embodiment, a database of digital slides or other images can be accessed to retrieve digital slides or other images that show characteristics similar to the digital slide under review.
- FIG. 5 is a network diagram illustrating a digital pathology system 500 for improved quality assurance in pathology according to an embodiment of the invention.
- the system 500 comprises a slide scanner 510 that is communicatively coupled with a slide reviewer station 520 via a network 530.
- the slide scanner 510 can be any of a variety of digital slide creation systems including image tiling systems, array scanning systems, or line scanning systems, including line scanning systems utilizing time-delay-integration ("TDI").
- the line scanning systems are preferred because they create digital slides more rapidly and also because the resulting digital slide images have a much higher quality both in terms of better focus and reduced artifacts such as stitching that are typically introduced by image tiling systems.
- the slide scanner functions to digitize a glass slide and store the digital slide in the data storage area 515. Also stored in the data storage area 515 are digital slide analysis tools and modules that can be implemented by the slide scanner 510 to assess the quality of a digital slide. Additionally, digital slide enhancement tools and modules that can be implemented by the slide scanner 510 to improve the quality of a digital slide are also stored in the data storage area 515. These analysis and enhancement tools may also be stored in a separate local or remote data storage area (not shown), for example to conserve processor power at the scanning station and to allow another device to perform the analysis and enhancement functions.
- the slide reviewer station 520 can be in communication with the slide scanner 510 either directly (not shown) or via the network 530, which may be a local or wide area network, public or private network, and may or may not include that global combination of networks that is commonly known as the Internet.
- the slide reviewer station 520 is configured with its own data storage area 525 and allows a pathologist or other analyst (e.g., histotechnologist) to review digital slides that are stored at the slide scanner 510 or at the slide reviewer station 520.
- slides are digitally scanned, their image quality is assessed and slides with sufficient quality are digitally enhanced and then subsequently sent via a network to the reviewing station of a pathologist for analysis.
- This entire process can be automated, for example by the presence of a barcode on the glass slide that provides information about where the send the enhanced digital slide image for analysis by the pathologist.
- FIG. 6 is a block diagram illustrating an example computer system 550 that may be used in connection with various embodiments described herein.
- the computer system 550 may be used in conjunction with the slide scanner system or slide reviewer system previously described with respect to FIG. 5 .
- Other computer systems and/or architectures may also be used, as will be clear to those skilled in the art.
- the computer system 550 preferably includes one or more processors, such as processor 552. Additional processors may be provided, such as an auxiliary processor to manage input/output, an auxiliary processor to perform floating point mathematical operations, a special-purpose microprocessor having an architecture suitable for fast execution of signal processing algorithms (e.g., digital signal processor), a slave processor subordinate to the main processing system (e.g., back-end processor), an additional microprocessor or controller for dual or multiple processor systems, or a coprocessor.
- auxiliary processors may be discrete processors or may be integrated with the processor 552.
- the processor 552 is preferably connected to a communication bus 554.
- the communication bus 554 may include a data channel for facilitating information transfer between storage and other peripheral components of the computer system 550.
- the communication bus 554 further may provide a set of signals used for communication with the processor 552, including a data bus, address bus, and control bus (not shown).
- the communication bus 554 may comprise any standard or non-standard bus architecture such as, for example, bus architectures compliant with industry standard architecture ("ISA”), extended industry standard architecture (“EISA”), Micro Channel Architecture (“MCA”), peripheral component interconnect (“PCI”) local bus, or standards promulgated by the Institute of Electrical and Electronics Engineers (“IEEE”) including IEEE 488 general-purpose interface bus (“GPIB”), IEEE 696/S-100, and the like.
- ISA industry standard architecture
- EISA extended industry standard architecture
- MCA Micro Channel Architecture
- PCI peripheral component interconnect
- IEEE Institute of Electrical and Electronics Engineers
- IEEE Institute of Electrical and Electronics Engineers
- GPIB general
- Computer system 550 preferably includes a main memory 556 and may also include a secondary memory 558.
- the main memory 556 provides storage of instructions and data for programs executing on the processor 552.
- the main memory 556 is typically semiconductor-based memory such as dynamic random access memory (“DRAM”) and/or static random access memory (“SRAM”).
- DRAM dynamic random access memory
- SRAM static random access memory
- Other semiconductor-based memory types include, for example, synchronous dynamic random access memory (“SDRAM”), Rambus dynamic random access memory (“RDRAM”), ferroelectric random access memory (“FRAM”), and the like, including read only memory (“ROM”).
- SDRAM synchronous dynamic random access memory
- RDRAM Rambus dynamic random access memory
- FRAM ferroelectric random access memory
- ROM read only memory
- the secondary memory 558 may optionally include a hard disk drive 560 and/or a removable storage drive 562, for example a floppy disk drive, a magnetic tape drive, a compact disc (“CD”) drive, a digital versatile disc (“DVD”) drive, etc.
- the removable storage drive 562 reads from and/or writes to a removable storage medium 564 in a well-known manner.
- Removable storage medium 564 may be, for example, a floppy disk, magnetic tape, CD, DVD, etc.
- the removable storage medium 564 is preferably a computer readable medium having stored thereon computer executable code (i.e., software) and/or data.
- the computer software or data stored on the removable storage medium 564 is read into the computer system 550 as electrical communication signals 578.
- secondary memory 558 may include other similar means for allowing computer programs or other data or instructions to be loaded into the computer system 550.
- Such means may include, for example, an external storage medium 572 and an interface 570.
- external storage medium 572 may include an external hard disk drive or an external optical drive, or and external magnetooptical drive.
- secondary memory 558 may include semiconductor-based memory such as programmable read-only memory (“PROM”), erasable programmable read-only memory (“EPROM”), electrically erasable read-only memory (“EEPROM”), or flash memory (block oriented memory similar to EEPROM). Also included are any other removable storage units 572 and interfaces 570, which allow software and data to be transferred from the removable storage unit 572 to the computer system 550.
- PROM programmable read-only memory
- EPROM erasable programmable read-only memory
- EEPROM electrically erasable read-only memory
- flash memory block oriented memory similar to EEPROM
- Computer system 550 may also include a communication interface 574.
- the communication interface 574 allows software and data to be transferred between computer system 550 and external devices (e.g. printers), networks, or information sources.
- external devices e.g. printers
- computer software or executable code may be transferred to computer system 550 from a network server via communication interface 574.
- Examples of communication interface 574 include a modem, a network interface card ("NIC"), a communications port, a PCMCIA slot and card, an infrared interface, and an IEEE 1394 fire-wire, just to name a few.
- Communication interface 574 preferably implements industry promulgated protocol standards, such as Ethernet IEEE 802 standards, Fiber Channel, digital subscriber line (“DSL”), asynchronous digital subscriber line (“ADSL”), frame relay, asynchronous transfer mode (“ATM”), integrated digital services network (“ISDN”), personal communications services (“PCS”), transmission control protocol/Internet protocol (“TCP/IP”), serial line Internet protocol/point to point protocol (“SLIP/PPP”), and so on, but may also implement customized or non-standard interface protocols as well.
- industry promulgated protocol standards such as Ethernet IEEE 802 standards, Fiber Channel, digital subscriber line (“DSL”), asynchronous digital subscriber line (“ADSL”), frame relay, asynchronous transfer mode (“ATM”), integrated digital services network (“ISDN”), personal communications services (“PCS”), transmission control protocol/Internet protocol (“TCP/IP”), serial line Internet protocol/point to point protocol (“SLIP/PPP”), and so on, but may also implement customized or non-standard interface protocols as well.
- Communication channel 576 carries signals 578 and can be implemented using a variety of wired or wireless communication means including wire or cable, fiber optics, conventional phone line, cellular phone link, wireless data communication link, radio frequency (RF) link, or infrared link, just to name a few.
- RF radio frequency
- Computer executable code i.e., computer programs or software
- main memory 556 and/or the secondary memory 558 are stored in the main memory 556 and/or the secondary memory 558.
- Computer programs can also be received via communication interface 574 and stored in the main memory 556 and/or the secondary memory 558.
- Such computer programs when executed, enable the computer system 550 to perform the various functions of the present invention as previously described.
- computer readable medium is used to refer to any media used to provide computer executable code (e.g., software and computer programs) to the computer system 550. Examples of these media include main memory 556, secondary memory 558 (including hard disk drive 560, removable storage medium 564, and external storage medium 572), and any peripheral device communicatively coupled with communication interface 574 (including a network information server or other network device). These computer readable mediums are means for providing executable code, programming instructions, and software to the computer system 550.
- the software may be stored on a computer readable medium and loaded into computer system 550 by way of removable storage drive 562, interface 570, or communication interface 574.
- the software is loaded into the computer system 550 in the form of electrical communication signals 578.
- the software when executed by the processor 552, preferably causes the processor 552 to perform the inventive features and functions previously described herein.
- ASICs application specific integrated circuits
- FPGAs field programmable gate arrays
- ASICs application specific integrated circuits
- FPGAs field programmable gate arrays
- DSP digital signal processor
- a general-purpose processor can be a microprocessor, but in the alternative, the processor can be any processor, controller, microcontroller, or state machine.
- a processor can also be implemented as a combination of computing devices, for example, a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.
- a software module can reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, a removable disk, a CD-ROM, or any other form of storage medium including a network storage medium.
- An exemplary storage medium can be coupled to the processor such the processor can read information from, and write information to, the storage medium.
- the storage medium can be integral to the processor.
- the processor and the storage medium can also reside in an ASIC.
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Description
- The present invention generally relates to pathology and microscopy and more particularly relates to improvements in quality assurance for pathology using digital microscopy.
- The diagnosis of glass microscope slides by a pathologist is known to be subjective. Many factors contribute to this lack of objectivity, including the training and skill of the pathologist and the quality of the glass slides from which the diagnosis was made. While use of tissue processing instruments and automatic staining equipment has increased the quality and consistency of slide preparations, a significant portion of glass slides that are read by pathologists are still suboptimal and may contribute to inaccurate interpretations.
- One of the possible contributing factors to the subjectivity of reading pathology slides is the lack of standardization of the microscope, a tool that has been in use for hundreds of years and which is not recognized as an approved medical device. Pathologists are free to use whatever microscope they want to read glass slides and are expected to know how to keep their microscope in optimal (Koehler) alignment, what objectives lenses with what numerical apertures are best suited for different specimen types, and to be aware when the bulb in their microscope needs to be replaced (because the color temperature of the illuminating light will change the color in the image they observe through the microscope). Many pathologists' microscopes are not maintained in optimal working condition or furnished with optimal objective lenses, thus compromising spatial details and color fidelity that may be essential to making more accurate diagnoses.
- Another likely contributing factor to the subjectivity of pathology is deficiencies in glass slide quality, which can include over- or under-staining (i.e., too dark or too light), tissue folds, sections that are too thick or too thin, bubbles, debris as well as variations in image quality observed between slides prepared by different autostainers. There is little a pathologist can do to overcome the challenges of a poorly prepared glass slides ("garbage in / garbage out"), other than to try to make adjustments in the optical properties of the microscope (adjust condenser, increase/decrease light) to try and ameliorate glass slide quality problems.
- Referring to
FIG. 1 , a flow diagram illustrating a conventional process for quality assurance using glass slides is shown. Initially, in step 100 a glass slide is prepared and then instep 110 the quality of the slide is inspected and assessed. In a typical laboratory, a histotechnologist screens the glass slides to assess slide quality, as shown instep 120, and rejects sub-optimal slides before they are read by a pathologist. Rejected slides result in re-cuts and the preparation of new, presumably higher quality, glass slides. In some cases, the slides can be fixed, e.g., by restaining if the staining is too light. This is shown instep 130. Finally, when a glass slide is acceptable, the slide is reviewed and interpreted by a pathologist instep 140. - This conventional process suffers from the inability of the histotechnologist to carefully review every area of a glass slide (some labs process hundreds or thousands of slides every day). The conventional process additionally suffers from the increasing shortage of qualified histotechnologists, and pressure on laboratories to continually improve productivity. Furthermore, the overall aging of the population and the associated increased incidence of cancer (and surgical biopsies) only exacerbate the challenges of quality-assuring glass slides before they are read by a pathologist due to the significant increase in the number of glass slides that are prepared.
- Therefore, what is needed is a system and method that overcomes these significant problems found in the conventional systems as described above.
-
US 2006/007345 A1 discloses a system and a method for assessing virtual microscope slide image quality, wherein in order to determine whether a virtual slide image has any out of focus areas and is therefore a candidate for manual inspection, the various focus points used to scan the virtual slide image are used to calculate a best fit surface for the virtual slide image and the distance of each focus point from the best fit surface is then calculated and the largest distance is compared to a predetermined value. - The present invention provides a computer implemented method for improved image quality assurance in pathology as defined in claim 1. Further embodiments of the method according to the present invention are described in the dependent claims.
- Accordingly, described herein are methods for improving quality assurance in pathology using digital slide tools for assessing slide quality to trigger (i) preparation of new glass slides, (ii) re-scanning of glass slides, or (iii) enhancement of digital slides prior to interpretation by the pathologist. Digital slides created by slide scanning instruments contribute to improved diagnosis by pathologists by providing an automatic, systematic, objective, and consistent means for digital slide creation and analysis, enabling the use of computer implemented image analysis and image correction tools.
- A digital pathology system (slide scanning instrument and software) assesses and improves the quality of a digital slide. The improved digital slide has a higher image quality that results in increased efficiency in the interpretation of such digital slides when they are viewed on a monitor by a pathologist. These improved digital slides yield a more objective diagnosis than reading the corresponding glass slide under a microscope.
- Other features and advantages of the present invention will become more readily apparent to those of ordinary skill in the art after reviewing the following detailed description and accompanying drawings.
- The details of the present invention, both as to its structure and operation, may be gleaned in part by study of the accompanying drawings, in which like reference numerals refer to like parts, and in which:
-
FIG. 1 is a flow diagram illustrating a conventional process for quality assurance using glass slides; -
FIG. 2 is a flow diagram illustrating a process for quality assurance using digital slides according to an embodiment of the invention; -
FIG. 3 is a flow diagram illustrating an alternative process for quality assurance using digital slides according to an embodiment of the invention; -
FIG. 4 is a flow diagram illustrating an alternative process for quality assurance using digital slides according to an embodiment of the invention; -
FIG. 5 is a network diagram illustrating a digital pathology system for improved quality assurance in pathology according to an embodiment of the invention; and -
FIG. 6 is a block diagram illustrating an example computer system that may be used in connection with various embodiments described herein. - Certain examples as disclosed herein provide for systems and methods for quality assurance in pathology. After reading this description it will become apparent to one skilled in the art how to implement the invention in various alternative embodiments and alternative applications. However, although various embodiments of the present invention will be described herein, it is understood that these embodiments are presented by way of example only, and not limitation. As such, this detailed description of various alternative embodiments should not be construed to limit the scope or breadth of the present invention as set forth in the appended claims.
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FIG. 2 is a flow diagram illustrating a process for quality assurance using digital slides. The illustrated process can be carried out by a digital pathology system such as that later described with respect toFIG. 5 . Initially, instep 200 the glass slide is prepared in the conventional manner. Next, instep 210 the glass slide is scanned (digitized) to create a high quality digital slide image of the glass slide at a diagnostic resolution for the tissue type. Once the digital slide is created, computer implemented digital slide analysis tools are automatically applied to the slide instep 220 to assess the quality of the digital slide image. For example, the color and focus of a digital slide can be analyzed by quality modules that consider image attributes that include the contrast, brightness and spatial resolution of individual and groups of pixels in the digital slide image. If the quality of the digital slide is insufficient, as determined instep 230, the corresponding glass slide can be rejected and an operator can prepare a new glass slide. If the quality of the digital slide is sufficient for diagnosis, as determined instep 230, then the digital slide can be analyzed and interpreted by a pathologist, who views the digital slide on the monitor at a local or remote viewing station. Alternatively, glass slides in which the quality of the corresponding digital slide is determined to be sufficient by the computer implemented digital slide analysis tools, could be interpreted by a pathologist using a microscope. - In one example, the digital slide quality assessment is made by comparing objective characteristics of the digital slide against a predetermined set of criteria. Advantageously, this provides a consistent and standard level of quality in any digital slide image that can be systematically applied to all digital slides destined for review by a pathologist.
- Additionally, in one example the digitizing and automatic assessment of the digital slide may be employed for the sole purpose of removing this task from the histotechnologist, thereby allowing that person to perform other tasks and improve efficiencies. In such an embodiment, the histologist may be notified of borderline quality slides in order to make the final determination of quality for a significantly fewer number of glass slides.
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FIG. 3 is a flow diagram illustrating an alternative process for quality assurance using digital slides. The illustrated process can be carried out by a digital pathology system such as that later described with respect toFIG. 5 . The process inFIG. 3 is initially similar to the process described with respect toFIG. 2 so only the differences will be described here. - Once the glass slide is prepared and digitized and analyzed by the digital slide analysis tools and quality modules, if the quality of the digital slide is insufficient, as determined in
step 330, the digital slide image can be rejected and an operator can rescan the glass slide. This can be more efficient if, for example, the digital slide image was rejected due to problems with focus or even problems with too much staining. In one example, a rescan of a glass slide with too much staining can be done with decreased light during scanning in order to account for the over staining. Advantageously, this saves significant time in the overall process and also saves the native tissue source and other goods used in glass slide preparation. - Once a digital image of sufficient quality is created, as determined in
step 330, the system next applies computer implemented digital slide enhancement tools to improve the quality of the digital slide image even further, as shown instep 340. For example, the colors of stains can be enhanced or even changed to provide more color contrast in counterstained samples. After the quality assured and image enhanced digital slide is ready, then instep 350 the digital slide can be analyzed and interpreted by a pathologist, who views the digital slide on the monitor at a local or remote reviewing station. - In one embodiment, when a digital slide meets the predetermined quality criteria and is then improved by computer implemented digital enhancement, the improved digital slide is fed into a clinical decision support system that guides the pathologist through the process of making an interpreting the slide in order to arrive at a diagnosis for the slide, or the case associated with the slide.
- A few variations in the process shown in
FIG. 3 are also possible. For example, if the image quality of the digital slide as determined instep 320 is poor then a new glass slide maybe prepared rather than rescanning the original glass slide. Additionally, providing digital enhancements to the digital slide image is not a necessary step in the process although it provides potentially significantly improved images and can facilitate a more accurate diagnosis by the pathologist. - In one embodiment, the quality assurance system described herein includes using the slide scanning instrument to assess the quality of the glass slide being scanned, and in the event that the glass slide fails predetermined quality criteria, the scanning parameters of the scanning instrument are modified to create a digital slide with improved quality. A slide that is over stained (too dark) would be automatically re-scanned with less light. The determination of whether the glass slide meets predetermined quality criteria can be achieved by initially scanning the glass slide at low or high power and then performing certain types of image analysis on the resulting image to determine, as in the above example, if the slide is too dark.
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FIG. 4 is a flow diagram illustrating an alternative process for quality assurance using digital slides according to an embodiment of the invention. The illustrated process can be carried out by a digital pathology system such as that later described with respect toFIG. 5 . Initially, in step 400 a glass slide is digitized and then instep 410 the digital slide is automatically evaluated against a set of predetermined criteria to assess the digital slide quality. Instep 420, slides that meet or exceed the objective baseline for digital slide quality are then digitally enhanced where possible and then the digital slide is provided to a pathologist for review and analysis, as shown instep 430. - Advantageously, the embodiment shown in
FIG. 4 is a highly streamlined computer implemented process. A plurality of slides may be provided to the digital microscopy system for automatic serial or parallel scanning that results in the digital slides being provided to a local or remote pathologist for analysis and diagnosis. - In one embodiment, examples of the types of enhancements made in
step 420 to improve the digital slide image prior to diagnosis by a pathologist include enhancement of contrast, color, elimination of defects, and the like including other image processing techniques. - For example, color space standardization can be used to transform the digital slide image into a standardized or non-standardized (and better) color space. Doing so can ensure that digital slides displayed on a monitor appear more consistent in color than the corresponding glass slides would appear under a microscope. Additionally, image processing can apply image enhancement filters (e.g., sharpening, deconvolution, etc.) to the digital slide to enhance spatial details that are not readily apparent to the naked eye. Also, quality assessments can be computed to provide the pathologist an objective computer-generated measure of digital slide quality that informs the pathologist about the underlying integrity of the digital slide. This can be particularly advantageous to a pathologist because knowing that the digital slide quality is suboptimal (e.g., because of poor sample preparation) can be helpful to a pathologist. For example, if the result of a diagnosis of a suboptimal digital slide required surgery, the pathologist may instead order a new glass slide to be prepared and digitized in order to conduct a second review and analysis of the tissue.
- Image pattern recognition can also be employed, for example, as part of a decision support system, to automatically identify for a pathologist those regions of a digital slide which have diagnostic significance. This can be very helpful and provide a pathologist with the ability to interrogate regions of one or more digital slides in priority order. Additionally, content based image retrieval can be extremely useful by providing the pathologist with previously diagnosed (i.e., "solved" cases) that have similar image patterns to the digital slide being analyzed. In one embodiment, a database of digital slides or other images can be accessed to retrieve digital slides or other images that show characteristics similar to the digital slide under review.
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FIG. 5 is a network diagram illustrating adigital pathology system 500 for improved quality assurance in pathology according to an embodiment of the invention. In the illustrated embodiment, thesystem 500 comprises aslide scanner 510 that is communicatively coupled with aslide reviewer station 520 via anetwork 530. - The
slide scanner 510 can be any of a variety of digital slide creation systems including image tiling systems, array scanning systems, or line scanning systems, including line scanning systems utilizing time-delay-integration ("TDI"). The line scanning systems are preferred because they create digital slides more rapidly and also because the resulting digital slide images have a much higher quality both in terms of better focus and reduced artifacts such as stitching that are typically introduced by image tiling systems. - The slide scanner functions to digitize a glass slide and store the digital slide in the
data storage area 515. Also stored in thedata storage area 515 are digital slide analysis tools and modules that can be implemented by theslide scanner 510 to assess the quality of a digital slide. Additionally, digital slide enhancement tools and modules that can be implemented by theslide scanner 510 to improve the quality of a digital slide are also stored in thedata storage area 515. These analysis and enhancement tools may also be stored in a separate local or remote data storage area (not shown), for example to conserve processor power at the scanning station and to allow another device to perform the analysis and enhancement functions. - The
slide reviewer station 520 can be in communication with theslide scanner 510 either directly (not shown) or via thenetwork 530, which may be a local or wide area network, public or private network, and may or may not include that global combination of networks that is commonly known as the Internet. Theslide reviewer station 520 is configured with its owndata storage area 525 and allows a pathologist or other analyst (e.g., histotechnologist) to review digital slides that are stored at theslide scanner 510 or at theslide reviewer station 520. - In one embodiment, slides are digitally scanned, their image quality is assessed and slides with sufficient quality are digitally enhanced and then subsequently sent via a network to the reviewing station of a pathologist for analysis. This entire process can be automated, for example by the presence of a barcode on the glass slide that provides information about where the send the enhanced digital slide image for analysis by the pathologist.
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FIG. 6 is a block diagram illustrating anexample computer system 550 that may be used in connection with various embodiments described herein. For example, thecomputer system 550 may be used in conjunction with the slide scanner system or slide reviewer system previously described with respect toFIG. 5 . Other computer systems and/or architectures may also be used, as will be clear to those skilled in the art. - The
computer system 550 preferably includes one or more processors, such asprocessor 552. Additional processors may be provided, such as an auxiliary processor to manage input/output, an auxiliary processor to perform floating point mathematical operations, a special-purpose microprocessor having an architecture suitable for fast execution of signal processing algorithms (e.g., digital signal processor), a slave processor subordinate to the main processing system (e.g., back-end processor), an additional microprocessor or controller for dual or multiple processor systems, or a coprocessor. Such auxiliary processors may be discrete processors or may be integrated with theprocessor 552. - The
processor 552 is preferably connected to a communication bus 554. The communication bus 554 may include a data channel for facilitating information transfer between storage and other peripheral components of thecomputer system 550. The communication bus 554 further may provide a set of signals used for communication with theprocessor 552, including a data bus, address bus, and control bus (not shown). The communication bus 554 may comprise any standard or non-standard bus architecture such as, for example, bus architectures compliant with industry standard architecture ("ISA"), extended industry standard architecture ("EISA"), Micro Channel Architecture ("MCA"), peripheral component interconnect ("PCI") local bus, or standards promulgated by the Institute of Electrical and Electronics Engineers ("IEEE") including IEEE 488 general-purpose interface bus ("GPIB"), IEEE 696/S-100, and the like. -
Computer system 550 preferably includes amain memory 556 and may also include asecondary memory 558. Themain memory 556 provides storage of instructions and data for programs executing on theprocessor 552. Themain memory 556 is typically semiconductor-based memory such as dynamic random access memory ("DRAM") and/or static random access memory ("SRAM"). Other semiconductor-based memory types include, for example, synchronous dynamic random access memory ("SDRAM"), Rambus dynamic random access memory ("RDRAM"), ferroelectric random access memory ("FRAM"), and the like, including read only memory ("ROM"). - The
secondary memory 558 may optionally include ahard disk drive 560 and/or aremovable storage drive 562, for example a floppy disk drive, a magnetic tape drive, a compact disc ("CD") drive, a digital versatile disc ("DVD") drive, etc. Theremovable storage drive 562 reads from and/or writes to aremovable storage medium 564 in a well-known manner.Removable storage medium 564 may be, for example, a floppy disk, magnetic tape, CD, DVD, etc. - The
removable storage medium 564 is preferably a computer readable medium having stored thereon computer executable code (i.e., software) and/or data. The computer software or data stored on theremovable storage medium 564 is read into thecomputer system 550 as electrical communication signals 578. - In alternative embodiments,
secondary memory 558 may include other similar means for allowing computer programs or other data or instructions to be loaded into thecomputer system 550. Such means may include, for example, anexternal storage medium 572 and aninterface 570. Examples ofexternal storage medium 572 may include an external hard disk drive or an external optical drive, or and external magnetooptical drive. - Other examples of
secondary memory 558 may include semiconductor-based memory such as programmable read-only memory ("PROM"), erasable programmable read-only memory ("EPROM"), electrically erasable read-only memory ("EEPROM"), or flash memory (block oriented memory similar to EEPROM). Also included are any otherremovable storage units 572 andinterfaces 570, which allow software and data to be transferred from theremovable storage unit 572 to thecomputer system 550. -
Computer system 550 may also include acommunication interface 574. Thecommunication interface 574 allows software and data to be transferred betweencomputer system 550 and external devices (e.g. printers), networks, or information sources. For example, computer software or executable code may be transferred tocomputer system 550 from a network server viacommunication interface 574. Examples ofcommunication interface 574 include a modem, a network interface card ("NIC"), a communications port, a PCMCIA slot and card, an infrared interface, and an IEEE 1394 fire-wire, just to name a few. -
Communication interface 574 preferably implements industry promulgated protocol standards, such as Ethernet IEEE 802 standards, Fiber Channel, digital subscriber line ("DSL"), asynchronous digital subscriber line ("ADSL"), frame relay, asynchronous transfer mode ("ATM"), integrated digital services network ("ISDN"), personal communications services ("PCS"), transmission control protocol/Internet protocol ("TCP/IP"), serial line Internet protocol/point to point protocol ("SLIP/PPP"), and so on, but may also implement customized or non-standard interface protocols as well. - Software and data transferred via
communication interface 574 are generally in the form of electrical communication signals 578. Thesesignals 578 are preferably provided tocommunication interface 574 via acommunication channel 576.Communication channel 576 carriessignals 578 and can be implemented using a variety of wired or wireless communication means including wire or cable, fiber optics, conventional phone line, cellular phone link, wireless data communication link, radio frequency (RF) link, or infrared link, just to name a few. - Computer executable code (i.e., computer programs or software) is stored in the
main memory 556 and/or thesecondary memory 558. Computer programs can also be received viacommunication interface 574 and stored in themain memory 556 and/or thesecondary memory 558. Such computer programs, when executed, enable thecomputer system 550 to perform the various functions of the present invention as previously described. - In this description, the term "computer readable medium" is used to refer to any media used to provide computer executable code (e.g., software and computer programs) to the
computer system 550. Examples of these media includemain memory 556, secondary memory 558 (includinghard disk drive 560,removable storage medium 564, and external storage medium 572), and any peripheral device communicatively coupled with communication interface 574 (including a network information server or other network device). These computer readable mediums are means for providing executable code, programming instructions, and software to thecomputer system 550. - In an embodiment that is implemented using software, the software may be stored on a computer readable medium and loaded into
computer system 550 by way ofremovable storage drive 562,interface 570, orcommunication interface 574. In such an embodiment, the software is loaded into thecomputer system 550 in the form of electrical communication signals 578. The software, when executed by theprocessor 552, preferably causes theprocessor 552 to perform the inventive features and functions previously described herein. - Various embodiments may also be implemented primarily in hardware using, for example, components such as application specific integrated circuits ("ASICs"), or field programmable gate arrays ("FPGAs"). Implementation of a hardware state machine capable of performing the functions described herein will also be apparent to those skilled in the relevant art. Various embodiments may also be implemented using a combination of both hardware and software.
- Furthermore, those of skill in the art will appreciate that the various illustrative logical blocks, modules, circuits, and method steps described in connection with the above described figures and the embodiments disclosed herein can often be implemented as electronic hardware, computer software, or combinations of both. To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and steps have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the overall system. Skilled persons can implement the described functionality in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the invention. In addition, the grouping of functions within a module, block, circuit or step is for ease of description. Specific functions or steps can be moved from one module, block or circuit to another without departing from the invention.
- Moreover, the various illustrative logical blocks, modules, and methods described in connection with the embodiments disclosed herein can be implemented or performed with a general purpose processor, a digital signal processor ("DSP"), an ASIC, FPGA or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general-purpose processor can be a microprocessor, but in the alternative, the processor can be any processor, controller, microcontroller, or state machine. A processor can also be implemented as a combination of computing devices, for example, a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.
- Additionally, the steps of a method or algorithm described in connection with the embodiments disclosed herein can be embodied directly in hardware, in a software module executed by a processor, or in a combination of the two. A software module can reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, a removable disk, a CD-ROM, or any other form of storage medium including a network storage medium. An exemplary storage medium can be coupled to the processor such the processor can read information from, and write information to, the storage medium. In the alternative, the storage medium can be integral to the processor. The processor and the storage medium can also reside in an ASIC.
- The above description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art.
Claims (11)
- A computer implemented method for improved quality assurance in pathology comprising:scanning a glass slide in accordance with a set of scanning parameters to create a digital slide image of a tissue sample, the tissue sample being disposed on the surface of the glass slide, wherein the tissue sample comprises at least one stain;digitally analyzing the digital slide image to assess the quality of the digital slide image;comparing the assessed quality of the digital slide image to a set of predetermined criteria;determining whether the quality of the digital slide image meets the set of predetermined criteria, wherein the determination comprises determining whether the slide is over-stained;if it is determined that the quality of the digital slide image meets the set of predetermined criteria, providing the digital slide image on a digital image viewer; andif it is determined that the slide is over-stained, automatically digitally rescanning the over-stained glass slide with less light to create a second digital slide image of the tissue sample.
- The method of claim 1, further comprising identifying a characteristic of the digital slide image and digitally enhancing the identified characteristic to create an enhanced digital slide image, wherein providing the digital slide image comprises providing the enhanced digital slide image.
- The method of claim 2, wherein digitally enhancing the identified characteristic to create an enhanced digital slide image includes at least one of enhancing a color of the digital slide image and enhancing a pattern identified in the digital slide image.
- The method of claim 2, wherein digitally enhancing the identified characteristic comprises transforming a first color in the digital slide image to a second color in the enhanced digital slide image.
- The method of claim 2, wherein digitally enhancing the identified characteristic to create an enhanced digital slide image comprises at least one of adjusting the contrast of the digital slide image, adjusting the spatial resolution of the digital slide image, and adjusting the balance of stains in the digital slide image.
- The method of claim 1, further comprising:determining a pattern in the digital slide image;searching a database of reference images for an image having a pattern that matches the determined pattern in the digital slide image;identifying a reference image having a pattern that matches the determined pattern in the digital slide image; andproviding the reference image on the digital image viewer in association with the digital slide image.
- The method of claim 1, wherein the resolution of the digital slide image is a diagnostic resolution for the tissue sample.
- The method of claim 1, further comprising:digitally analyzing the second digital slide image to assess the quality of the second digital slide image;comparing the assessed quality of the second digital slide image to the set of predetermined criteria;determining that the quality of the second digital slide image meets the set of predetermined criteria; andproviding the second digital slide image on a digital image viewer.
- The method of claim 1, wherein providing the digital slide image on a digital image viewer comprises sending the digital slide image to a remote reviewing station via a network.
- The method of claim 9, wherein sending the digital slide image comprises determining a destination of the digital slide image based on information provided in a barcode on the glass slide.
- The method of claim 1, further comprising providing an objective computer-generated measure of the quality of the digital slide image to the pathologist.
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Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008137667A1 (en) * | 2007-05-04 | 2008-11-13 | Aperio Technologies, Inc. | System and method for quality assurance in pathology |
WO2010115089A2 (en) * | 2009-04-03 | 2010-10-07 | University Of Virginia Patent Foundation | Serial multiple antigen colocalization in paraffin-embedded tissue |
WO2010148152A2 (en) * | 2009-06-16 | 2010-12-23 | Ikonisys, Inc. | System and method for remote control of a microscope |
US20110135144A1 (en) * | 2009-07-01 | 2011-06-09 | Hand Held Products, Inc. | Method and system for collecting voice and image data on a remote device and coverting the combined data |
US8891851B2 (en) * | 2009-07-15 | 2014-11-18 | Glenn F. Spaulding | Home healthcare management system and hardware |
US8504726B2 (en) | 2009-07-27 | 2013-08-06 | Corista LLC | User targeted medical imaging and information packaging, compression and distribution system |
US8244912B2 (en) | 2009-07-27 | 2012-08-14 | Coritsa LLC | System for networked digital pathology exchange |
US8463741B2 (en) * | 2009-09-04 | 2013-06-11 | Omnyx, LLC | Digital pathology system |
JP5627698B2 (en) | 2009-10-19 | 2014-11-19 | ベンタナ メディカル システムズ, インコーポレイテッド | Imaging system and technique |
US8396269B2 (en) | 2010-04-08 | 2013-03-12 | Digital Pathco LLC | Image quality assessment including comparison of overlapped margins |
WO2011153500A2 (en) | 2010-06-04 | 2011-12-08 | Aperio Technologies, Inc. | System and method to determine slide quality of a digitized microscope slide |
WO2012037416A1 (en) | 2010-09-16 | 2012-03-22 | Omnyx, LLC | Histology workflow management system |
US8934718B2 (en) | 2011-08-02 | 2015-01-13 | Nec Laboratories America, Inc. | Interactive analytics of digital histology slides |
EP4321889A3 (en) | 2012-03-19 | 2024-03-20 | Genetic Innovations Inc. | Devices, systems, and methods for virtual staining |
US20140244283A1 (en) | 2013-02-25 | 2014-08-28 | Complete Consent, Llc | Pathology, radiology and other medical or surgical specialties quality assurance |
US12080406B2 (en) | 2013-02-25 | 2024-09-03 | Complete Consent, Llc | Tracking and quality assurance of pathology, radiology and other medical or surgical procedures |
US10209165B2 (en) | 2014-03-10 | 2019-02-19 | Visiopharm A/S | Assessment of staining quality |
US9336593B2 (en) | 2014-09-25 | 2016-05-10 | Cerner Innovation, Inc. | Methods for automated tissue sample processing and imaging |
US9488552B2 (en) | 2014-09-25 | 2016-11-08 | Cerner Innovation, Inc. | Cutting apparatus for automated tissue sample processing and imaging |
US9600876B2 (en) | 2014-09-25 | 2017-03-21 | Cerner Innovation, Inc. | Systems for automated tissue sample processing and imaging |
US20160239962A1 (en) * | 2015-02-13 | 2016-08-18 | Prairie Ventures, Llc | System and method to objectively measure quality assurance in anatomic pathology |
WO2016189065A1 (en) * | 2015-05-26 | 2016-12-01 | Ventana Medical Systems, Inc. | Method and system for assessing stain quality for in-situ hybridization and immunohistochemistry |
AU2016269085B2 (en) * | 2015-05-26 | 2019-12-19 | Ventana Medical Systems, Inc. | Method and system for assessing stain quality for in-situ hybridization and immunohistochemistry |
ES2842883T3 (en) * | 2015-12-18 | 2021-07-15 | Abbott Lab | Methods and systems for evaluating histological stains |
EP3662407B8 (en) * | 2017-08-03 | 2025-06-25 | Nucleai Ltd | Systems and methods for analysis of tissue images |
JP2020202748A (en) * | 2017-08-31 | 2020-12-24 | 富士フイルム株式会社 | Photographing processing apparatus, control method of photographing processing apparatus, and photographing processing program |
JP7119085B2 (en) * | 2017-11-30 | 2022-08-16 | ライカ バイオシステムズ イメージング インコーポレイテッド | Impact rescan system |
CN108492289B (en) * | 2018-03-19 | 2021-09-10 | 上海宝谊图片有限公司 | Digital image quality evaluation system |
WO2020091965A2 (en) | 2018-11-02 | 2020-05-07 | Hologic, Inc. | Digital imaging system and method |
US11193950B2 (en) | 2019-03-29 | 2021-12-07 | Sakura Finetek U.S.A., Inc. | Slide identification sensor |
WO2020257939A1 (en) | 2019-06-26 | 2020-12-30 | Pathcore Inc. | Devices for inspecting adequate exposure of a tissue sample to a treatment medium and methods and uses therefor |
JP2022111743A (en) * | 2021-01-20 | 2022-08-01 | 株式会社ニコン | Image processing method, program, image processing apparatus |
US11455724B1 (en) * | 2021-05-12 | 2022-09-27 | PAIGE.AI, Inc. | Systems and methods to process electronic images to adjust attributes of the electronic images |
CN115880233A (en) * | 2022-11-28 | 2023-03-31 | 广州金域医学检验中心有限公司 | Cytopathological image evaluation method and device |
US12394032B1 (en) * | 2025-02-11 | 2025-08-19 | Pramana, Inc. | Apparatus and method for rescan workflow management in automated scanning systems |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040101177A1 (en) * | 2002-11-21 | 2004-05-27 | Siemens Aktiengesellschaft | Method and system for retrieving a medical picture |
Family Cites Families (88)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3643015A (en) | 1970-06-19 | 1972-02-15 | Paul Davidovits | Scanning optical microscope |
US4420566A (en) * | 1982-06-10 | 1983-12-13 | Eastman Kodak Company | Method and apparatus for detecting sample fluid on an analysis slide |
US4742558A (en) | 1984-02-14 | 1988-05-03 | Nippon Telegraph & Telephone Public Corporation | Image information retrieval/display apparatus |
DE3577355D1 (en) | 1984-06-25 | 1990-05-31 | Olympus Optical Co | MICROSCOPE. |
US4700298A (en) | 1984-09-14 | 1987-10-13 | Branko Palcic | Dynamic microscope image processing scanner |
US4673988A (en) | 1985-04-22 | 1987-06-16 | E.I. Du Pont De Nemours And Company | Electronic mosaic imaging process |
US4760385A (en) | 1985-04-22 | 1988-07-26 | E. I. Du Pont De Nemours And Company | Electronic mosaic imaging process |
JPH0652263B2 (en) * | 1985-12-10 | 1994-07-06 | 株式会社日立製作所 | Cell analyzer |
US4777525A (en) | 1985-12-23 | 1988-10-11 | Preston Jr Kendall | Apparatus and method for a multi-resolution electro-optical imaging, display and storage/retrieval system |
US4845552A (en) | 1987-08-20 | 1989-07-04 | Bruno Jaggi | Quantitative light microscope using a solid state detector in the primary image plane |
US5740270A (en) | 1988-04-08 | 1998-04-14 | Neuromedical Systems, Inc. | Automated cytological specimen classification system and method |
JP2749069B2 (en) | 1988-04-26 | 1998-05-13 | オリンパス光学工業株式会社 | Fluorescence microscope equipment |
US5067152A (en) | 1989-01-30 | 1991-11-19 | Information Technologies Research, Inc. | Method and apparatus for vector quantization |
US4960999A (en) | 1989-02-13 | 1990-10-02 | Kms Fusion, Inc. | Scanning and storage of electrophoretic records |
US4987480A (en) | 1989-07-11 | 1991-01-22 | Massachusetts Institute Of Technology | Multiscale coding of images |
US5086477A (en) | 1990-08-07 | 1992-02-04 | Northwest Technology Corp. | Automated system for extracting design and layout information from an integrated circuit |
US5231663A (en) | 1991-03-18 | 1993-07-27 | Earl Joseph G | Image processing system |
US5187754A (en) | 1991-04-30 | 1993-02-16 | General Electric Company | Forming, with the aid of an overview image, a composite image from a mosaic of images |
US5790710A (en) | 1991-07-12 | 1998-08-04 | Jeffrey H. Price | Autofocus system for scanning microscopy |
US5172228A (en) | 1991-11-19 | 1992-12-15 | Utah State University Foundation | Image compression method and apparatus employing distortion adaptive tree search vector quantization |
US5495535A (en) | 1992-01-31 | 1996-02-27 | Orbotech Ltd | Method of inspecting articles |
US5912699A (en) | 1992-02-18 | 1999-06-15 | Neopath, Inc. | Method and apparatus for rapid capture of focused microscopic images |
US5448399A (en) | 1992-03-13 | 1995-09-05 | Park Scientific Instruments | Optical system for scanning microscope |
JPH05264221A (en) | 1992-03-17 | 1993-10-12 | Fujitsu Ltd | Device for detecting mark position for semiconductor exposure device and positioning deice for semiconductor exposure device using the same |
JP3275368B2 (en) | 1992-07-09 | 2002-04-15 | 株式会社ニコン | Exposure method and apparatus |
US5633948A (en) | 1992-11-30 | 1997-05-27 | Kegelmeyer, Jr.; W. Philip | Method and apparatus for detecting a desired behavior in digital image data |
US5479252A (en) | 1993-06-17 | 1995-12-26 | Ultrapointe Corporation | Laser imaging system for inspection and analysis of sub-micron particles |
US5483055A (en) | 1994-01-18 | 1996-01-09 | Thompson; Timothy V. | Method and apparatus for performing an automatic focus operation for a microscope |
US5793969A (en) | 1993-07-09 | 1998-08-11 | Neopath, Inc. | Network review and analysis of computer encoded slides |
GB2286309B (en) | 1994-02-01 | 1998-04-15 | Rank Cintel Ltd | High resolution film scanner |
US5578832A (en) | 1994-09-02 | 1996-11-26 | Affymetrix, Inc. | Method and apparatus for imaging a sample on a device |
US5638459A (en) * | 1994-09-20 | 1997-06-10 | Neopath, Inc. | Method and apparatus for detecting a microscope slide coverslip |
US5649032A (en) | 1994-11-14 | 1997-07-15 | David Sarnoff Research Center, Inc. | System for automatically aligning images to form a mosaic image |
US5625706A (en) * | 1995-05-31 | 1997-04-29 | Neopath, Inc. | Method and apparatus for continously monitoring and forecasting slide and specimen preparation for a biological specimen population |
US5671288A (en) * | 1995-05-31 | 1997-09-23 | Neopath, Inc. | Method and apparatus for assessing slide and specimen preparation quality |
US5922282A (en) | 1995-06-07 | 1999-07-13 | Ledley; Robert S. | Super fast tuberculosis diagnosis and sensitivity testing method |
JP2000501844A (en) | 1995-07-19 | 2000-02-15 | モルフォメトリックス テクノロジーズ インク. | Automatic scanning of microscope slides |
KR987001186A (en) | 1995-10-18 | 1998-04-30 | 요트.게.아.롤페즈 | Region-based Texture Coding and Decoding Method, and Corresponding System (Region-Based Texture Coding and Decoding Method, and Corresponding Systems) |
US5710835A (en) | 1995-11-14 | 1998-01-20 | The Regents Of The University Of California, Office Of Technology Transfer | Storage and retrieval of large digital images |
EP0864082B1 (en) * | 1995-11-30 | 2003-04-02 | Chromavision Medical Systems, Inc. | Method for automated image analysis of biological specimens |
US6005964A (en) | 1996-01-24 | 1999-12-21 | The Board Of Trustees Of The University Of Illinois | Automatic machine vision microscope slide inspection system and method |
US5872591A (en) | 1996-02-21 | 1999-02-16 | Pakon, Inc. | Film scanner |
US6078681A (en) | 1996-03-18 | 2000-06-20 | Marine Biological Laboratory | Analytical imaging system and process |
US6091846A (en) | 1996-05-31 | 2000-07-18 | Texas Instruments Incorporated | Method and system for anomaly detection |
AU3723697A (en) | 1996-07-12 | 1998-02-09 | Erim International, Inc. | Mosaic construction, processing, and review of very large electronic micrograph composites |
US6031930A (en) | 1996-08-23 | 2000-02-29 | Bacus Research Laboratories, Inc. | Method and apparatus for testing a progression of neoplasia including cancer chemoprevention testing |
US6272235B1 (en) | 1997-03-03 | 2001-08-07 | Bacus Research Laboratories, Inc. | Method and apparatus for creating a virtual microscope slide |
GB9622055D0 (en) | 1996-10-23 | 1996-12-18 | Univ Strathclyde | Vector quantisation |
EP0936855A1 (en) * | 1996-10-25 | 1999-08-25 | Monsanto Company | Composition and method for treating plants with exogenous chemicals |
US5968731A (en) | 1996-12-10 | 1999-10-19 | The Regents Of The University Of California | Apparatus for automated testing of biological specimens |
US20010017941A1 (en) | 1997-03-14 | 2001-08-30 | Navin Chaddha | Method and apparatus for table-based compression with embedded coding |
DE19714221A1 (en) | 1997-04-07 | 1998-10-08 | Zeiss Carl Fa | Confocal microscope with a motorized scanning table |
US6002789A (en) | 1997-06-24 | 1999-12-14 | Pilot Industries, Inc. | Bacteria colony counter and classifier |
US6198839B1 (en) * | 1997-09-05 | 2001-03-06 | Tripath Imaging, Inc. | Dynamic control and decision making method and apparatus |
JPH1196334A (en) * | 1997-09-17 | 1999-04-09 | Olympus Optical Co Ltd | Image processor |
JP4253381B2 (en) * | 1997-12-02 | 2009-04-08 | オリンパス株式会社 | Electronic camera for microscope |
US5943122A (en) | 1998-07-10 | 1999-08-24 | Nanometrics Incorporated | Integrated optical measurement instruments |
JP3139998B2 (en) | 1998-12-01 | 2001-03-05 | 株式会社東京精密 | Appearance inspection device and method |
US6330348B1 (en) | 1999-01-21 | 2001-12-11 | Resolution Sciences Corporation | Method and apparatus for measurement of microtome performance |
JP4323608B2 (en) | 1999-03-12 | 2009-09-02 | キヤノン株式会社 | Exposure apparatus and device manufacturing method |
US7212667B1 (en) | 1999-05-17 | 2007-05-01 | Samsung Electronics Co., Ltd. | Color image processing method for indexing an image using a lattice structure |
JP4441831B2 (en) * | 1999-09-16 | 2010-03-31 | 株式会社ニコン | Microscope equipment |
US7668362B2 (en) * | 2000-05-03 | 2010-02-23 | Aperio Technologies, Inc. | System and method for assessing virtual slide image quality |
US6711283B1 (en) | 2000-05-03 | 2004-03-23 | Aperio Technologies, Inc. | Fully automatic rapid microscope slide scanner |
US6656683B1 (en) * | 2000-07-05 | 2003-12-02 | Board Of Regents, The University Of Texas System | Laser scanning cytology with digital image capture |
JP2003163833A (en) * | 2001-11-28 | 2003-06-06 | Olympus Optical Co Ltd | Microscope use imaging apparatus |
JP2003230154A (en) * | 2002-01-31 | 2003-08-15 | Olympus Optical Co Ltd | Digital camera for microscope |
US6947869B2 (en) | 2002-03-29 | 2005-09-20 | The United States Of America As Represented By The Secretary Of The Navy | Efficient near neighbor search (ENN-search) method for high dimensional data sets with noise |
US20050142654A1 (en) * | 2002-10-18 | 2005-06-30 | Kazuji Matsumoto | Slide glass, cover glass and pathologic diagnosis system |
US20040122708A1 (en) * | 2002-12-18 | 2004-06-24 | Avinash Gopal B. | Medical data analysis method and apparatus incorporating in vitro test data |
US7257268B2 (en) * | 2003-02-28 | 2007-08-14 | Aperio Technologies, Inc. | Systems and methods for image pattern recognition |
US8185317B2 (en) * | 2003-06-12 | 2012-05-22 | Cytyc Corporation | Method and system of determining the stain quality of slides using scatter plot distribution |
JP4508569B2 (en) * | 2003-07-29 | 2010-07-21 | オリンパス株式会社 | Binocular stereoscopic observation device, electronic image stereoscopic microscope, electronic image stereoscopic observation device, electronic image observation device |
EP1680757A4 (en) * | 2003-10-08 | 2006-11-22 | Lifespan Biosciences Inc | Automated microspcope slide tissue sample mapping and image acquisition |
JP4725102B2 (en) * | 2004-12-28 | 2011-07-13 | コニカミノルタエムジー株式会社 | Image processing method, image processing apparatus, and image processing program |
US20060159325A1 (en) * | 2005-01-18 | 2006-07-20 | Trestle Corporation | System and method for review in studies including toxicity and risk assessment studies |
CA2595248A1 (en) * | 2005-01-18 | 2006-07-27 | Trestle Corporation | System and method for creating variable quality images of a slide |
JP2006209698A (en) * | 2005-01-31 | 2006-08-10 | Olympus Corp | Target tracking device, microscope system and target tracking program |
US20060178833A1 (en) * | 2005-02-04 | 2006-08-10 | Bauer Kenneth D | System for and method of providing diagnostic information through microscopic imaging |
US7720268B2 (en) * | 2005-07-15 | 2010-05-18 | Siemens Corporation | System and method for ultrasound specific segmentation using speckle distributions |
US7899624B2 (en) * | 2005-07-25 | 2011-03-01 | Hernani Del Mundo Cualing | Virtual flow cytometry on immunostained tissue-tissue cytometer |
US7657070B2 (en) * | 2006-01-20 | 2010-02-02 | Sakura Finetek U.S.A., Inc. | Automated system of processing biological specimens and method |
US20080009707A1 (en) * | 2006-06-15 | 2008-01-10 | Theriault Richard H | Three-dimensional rendering of MRI results using automatic segmentation |
WO2008061548A1 (en) * | 2006-11-22 | 2008-05-29 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Reconstruction and visualization of neuronal cell structures with brigh-field mosaic microscopy |
US20080166036A1 (en) * | 2007-01-05 | 2008-07-10 | Carl Zeiss Microimaging Ais, Inc. | System and method for analyzing tissue slides for observable pathologies |
JP5131431B2 (en) * | 2007-01-26 | 2013-01-30 | 日本電気株式会社 | Pathological image evaluation apparatus, pathological image evaluation method, and pathological image evaluation program |
US7876940B2 (en) * | 2007-01-30 | 2011-01-25 | International Business Machines Corporation | Universal image processing |
WO2008137667A1 (en) | 2007-05-04 | 2008-11-13 | Aperio Technologies, Inc. | System and method for quality assurance in pathology |
-
2008
- 2008-05-02 WO PCT/US2008/062407 patent/WO2008137667A1/en active Application Filing
- 2008-05-02 JP JP2010507550A patent/JP5389016B2/en active Active
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040101177A1 (en) * | 2002-11-21 | 2004-05-27 | Siemens Aktiengesellschaft | Method and system for retrieving a medical picture |
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